RESUMO
The data presented in this article are related to the research article entitled "Retinoic acid induces hypersegmentation and enhances cytotoxicity of neutrophils against cancer cells" (S. Shrestha, S.Y. Kim, Y.J. Young, J.K. Kim, J.M. Lee, M. Shin, D.K. Song, C.W. Hong, 2017) [1]. This article complements the potential of retinoic acid to induce changes in effector function of human neutrophils. Here the datasets describe the rate of apoptosis, changes in numbers of nuclear lobes, and the expressions of surface markers in human neutrophils in presence or absence of retinoic acid. The tumor growth in recipient mice with adoptive transfer of retinoic acid-treated neutrophils was evaluated. The included data is made publicly available to criticism and extended analysis.
RESUMO
Hypersegmentation of nuclei is considered a distinct characteristic of the antitumoral phenotype of neutrophils. Retinoic acid, a metabolite of retinol, reorganizes and induces segmentation of the nucleus during the differentiation of neutrophils. However, the role of retinoic acid in the phenotype polarization of neutrophils has not been fully established. Here, we investigated the effect of retinoic acid on phenotype polarization of neutrophils. Retinoic acid-induced the hypersegmentation of human neutrophils via retinoic acid receptors and mTOR pathways. Retinoic acid-induced hypersegmented neutrophils enhanced neutrophil extracellular traps (NETs) formation in response to phorbol-12-myristate 13-acetate (PMA) and fMLP (N-Formylmethionine-leucyl-phenylalanine) stimulation, and increased cytotoxicity against various tumor cells. Moreover, retinoic acid treatment attenuated tumor growth in a murine model of tumor. Taken together, these results suggests that retinoic acid induces the phenotype polarization of neutrophils to exert antitumor effects.
Assuntos
Citotoxicidade Imunológica/efeitos dos fármacos , Transtornos Leucocíticos/induzido quimicamente , Neoplasias/imunologia , Neoplasias/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Tretinoína/farmacologia , Animais , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/imunologia , Feminino , Humanos , Transtornos Leucocíticos/imunologia , Transtornos Leucocíticos/metabolismo , Camundongos , Neoplasias/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Espécies Reativas de Oxigênio , Receptores do Ácido Retinoico/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genéticaRESUMO
Tumor microenvironments polarize neutrophils to protumoral phenotypes. Here, we demonstrate that the angiotensin converting enzyme inhibitors (ACEis) and angiotensin II type 1 receptor (AGTR1) antagonist attenuate tumor growth via polarization of neutrophils toward an antitumoral phenotype. The ACEis or AGTR1 antagonist enhanced hypersegmentation of human neutrophils and increased neutrophil cytotoxicity against tumor cells. This neutrophil hypersegmentation was dependent on the mTOR pathway. In a murine tumor model, ACEis and AGTR1 antagonist attenuated tumor growth and enhanced neutrophil hypersegmentation. ACEis inhibited tumor-induced polarization of neutrophils to a protumoral phenotype. Neutrophil depletion reduced the antitumor effect of ACEi. Together, these data suggest that the modulation of Ang II pathway attenuates tumor growth via polarization of neutrophils to an antitumoral phenotype.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: In Korean medicine, the steamed root of Panax ginseng C.A. Meyer, known as Korean red ginseng (KRG), is used to invigorate the body, enhance qi, and improve blood flow. It is a potential treatment for cold hypersensitivity in the hands and feet (CHHF), a common complaint among Asians, especially women. However, few studies of its efficacy and safety for CHHF have been conducted. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial included 80 female patients with CHHF at Kyung Hee University Hospital at Gangdong, Seoul, Korea. The participants took six capsules of 500-mg KRG powder or placebo twice daily for 8 weeks and were followed up for 4 weeks. The primary outcome measure was change in skin temperature of the hands. The secondary outcome measures included change in skin temperature of the feet, visual analog scale (VAS) scores of CHHF severity, recovered temperature (RT) of the hands after cold stress test, distal-dorsal difference (DDD) in temperature of the hands, power variables of heart rate variability (HRV), and 36-item Short-Form Health Survey (SF-36) scores. RESULTS: The KRG group had significantly higher skin temperature of the hands and feet, lower VAS scores, higher RT of the right 5th finger, and less parasympathetic activity than the placebo group at 8 weeks. No significant differences were noted in DDD of the hands and SF-36 scores. No serious adverse events were reported during the study. CONCLUSIONS: Peripheral vasodilation by KRG may alleviate CHHF. Further controlled studies are required to elucidate the effects of KRG on the autonomic nervous system.